@Little Beard: Correct. Avellone has stated the Courier had done something. I don't know though.
He certainly implied the Courier may have done something to set Ulysses off, but yeah, I think it's a pretty safe bet that it was an action the Courier took.
It was also stated the relationship between them would be greatly unexpected. We can cross out things such as; relatives, lovers, etc. It is greatly shrouded. But we know the Courier knows the Lonesome Road, since Ulysses stated he knows the way.
I formerly believed that the Courier might be from this region. Possibly originating from the town of Hopeville.
I'm now beginning to think that the Courier might not be from there at all, but that he knows the area because he once made a delivery there. A package, with something in it. Something that the Courier delivered blindly. Some sort of homing beacon or some other bit of technology that allowed the Think Tank to target that region for the meteorological experiment that ripped the region apart.